tbuckley/cabot-search huggingface dataset:
Targeting the stem cell niche: role of collagen XVII in skin aging and wound repair
Authors: Yangdan Liu, Chiakang Ho, Dongsheng Wen, Jiaming Sun, Lu Huang, Ya Gao, Qingfeng Li, Yifan Zhang
Journal: Theranostics (2022)

The skin epidermis and appendages undergo ongoing renewal throughout life.Stem cells residing in the epidermis and hair follicles are pivotal for sustaining skin homeostasis.The self-renewal ability of stem cells significantly decreases during skin aging but actively increases during wound repair.Residential stem cells reside in niches that provide spatially distinct microenvironments for stem cell maintenance and function.Cell-extracellular matrix (ECM) adhesion is essential for the establishment of niche architecture.Collagen XVII (COL17), as a transmembrane protein constituting hemidesmosomes (HDs), mediates the interactions of stem cells with surrounding cells and the matrix to regulate skin homeostasis, aging and wound repair.This review focuses on the pivotal role of the niche component COL17 in stem cell maintenance and its function in regulation of skin aging and wound repair.
Polyglutamate-based nanoconjugates for image-guided surgery and post-operative melanoma metastases prevention
Authors: Yana Epshtein, Rachel Blau, Evgeni Pisarevsky, Shani Koshrovski-Michael, Dikla Ben-Shushan, Sabina Pozzi, Gal Shenbach-Koltin, Lidar Fridrich, Marina Buzhor, Adva Krivitsky, Pradip Dey, Ronit Satchi-Fainaro
Journal: Theranostics (2022)

Cutaneous melanoma is the most aggressive and deadliest of all skin malignancies. Complete primary tumor removal augmented by advanced imaging tools and effective post-operative treatment is critical in the prevention of tumor recurrence and future metastases formation.
Nanozyme-based colorimetric biosensor with a systemic quantification algorithm for noninvasive glucose monitoring
Authors: Hee-Jae Jeon, Hyung Shik Kim, Euiheon Chung, Dong Yun Lee
Journal: Theranostics (2022)

Diabetes mellitus accompanies an abnormally high glucose level in the bloodstream.Early diagnosis and proper glycemic management of blood glucose are essential to prevent further progression and complications.Biosensor-based colorimetric detection has progressed and shown potential in portable and inexpensive daily assessment of glucose levels because of its simplicity, low-cost, and convenient operation without sophisticated instrumentation.Colorimetric glucose biosensors commonly use natural enzymes that recognize glucose and chromophores that detect enzymatic reaction products.However, many natural enzymes have inherent defects, limiting their extensive application.Recently, nanozyme-based colorimetric detection has drawn attention due to its merits including high sensitivity, stability under strict reaction conditions, flexible structural design with low-cost materials, and adjustable catalytic activities.This review discusses various nanozyme materials, colorimetric analytic methods and mechanisms, recent machine learning based analytic methods, quantification systems, applications and future directions for monitoring and managing diabetes.
Safety and efficacy of peptide receptor radionuclide therapy with <sup>177</sup>Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors
Authors: Yuanyuan Jiang, Qingxing Liu, Guochang Wang, Huimin Sui, Rongxi Wang, Jiarou Wang, Jingjing Zhang, Zhaohui Zhu, Xiaoyuan Chen
Journal: Theranostics (2022)

Rationale: This study aimed to assess the safety, efficacy, and survival of 177Lu-DOTA-EB-TATE in patients with metastatic neuroendocrine tumors (NETs).Methods: Thirty patients with metastatic NETs were prospectively enrolled and treated with 177Lu-DOTA-EB-TATE (3 intended cycles at 8 to 12-week intervals, 3.7 GBq/cycle). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The treatment response was graded according to RECIST 1.1 and PERCIST 1.0 criteria. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS). Results: Patients tolerated therapy well without acute adverse effects. During peptide receptor radionuclide therapy (PRRT), no grade 4 toxicity was observed in any of the patients; grade 3 hematotoxicity was recorded in 4 patients, including grade 3 thrombocytopenia in 4 patients (13.3%) and grade-3 anemia in 1 patient (3.3%); grade 3 hepatotoxicity was recorded in 1 (3.3%) patient, and no grade 2/3/4 nephrotoxicity was observed. On long-term follow-up, none of the patients developed grade 4 hematotoxicity or nephrotoxicity of any grade, reversible grade 3 hematotoxicity (thrombocytopenia) occurred in 1 patient. There was no incidence of leukemia or myelodysplastic syndrome for the duration of follow-up. Of 27 patients with RECIST-measurable disease, partial response and stable disease were seen in 9 and 14 patients, respectively, resulting in a response rate of 33.3% and disease control rate of 85.2%. Of 29 patients evaluable for response on 68Ga-DOTATATE PET/CT, 14 had partial response and 11 had stable disease, with a response rate of 48.3% and disease control rate of 86.2%. The follow-up period ranged from 5 to 57 months after the first 177Lu-DOTA-EB-TATE PRRT with a median follow-up of 46 months. The median PFS was 36 months, and the median OS was not reached. Ki-67 index of greater than 10% was associated with poorer PFS (P = 0.012). Conclusions: Our results suggest that PRRT with approximately 3.7 GBq 177Lu-DOTA-EB-TATE has acceptable toxicity profile and is effective in treating metastatic NET with high disease control rate. In addition, 177Lu-DOTA-EB-TATE achieved a favorable survival outcome with encouraging PFS.
<sup>18</sup>F-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis
Authors: Yuchen Jiang, Qinghe Zeng, Qinghui Jiang, Xia Peng, Jing Gao, Haiyan Wan, Luting Wang, Yinglei Gao, Xiaoyu Zhou, Dongze Lin, Hanyi Feng, Sheng Liang, Hu Zhou, Jian Ding, Jing Ai, Ruimin Huang
Journal: Theranostics (2022)

Rationale:The overall clinical response to FGFR inhibitor (FGFRi) is far from satisfactory in cancer patients stratified by FGFR aberration, the current biomarker in clinical practice.A novel biomarker to evaluate the therapeutic response to FGFRi in a non-invasive and dynamic manner is thus greatly desired.Methods: Six FGFR-aberrant cancer cell lines were used, including four FGFRi-sensitive ones (NCI-H1581, NCI-H716, RT112 and Hep3B) and two FGFRi-resistant ones (primary for NCI-H2444 and acquired for NCI-H1581/AR).Cell viability and tumor xenograft growth analyses were performed to evaluate FGFRi sensitivities, accompanied by corresponding 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake assay.mTOR/PLCγ/MEK-ERK signaling blockade by specific inhibitors or siRNAs was applied to determine the regulation mechanism.Results: FGFR inhibition decreased the in vitro accumulation of 18 F-FDG only in four FGFRi-sensitive cell lines, but in neither of FGFRi-resistant ones.We then demonstrated that FGFRi-induced transcriptional downregulation of hexokinase 2 (HK2), a key factor of glucose metabolism and FDG trapping, via mTOR pathway leading to this decrease.Moreover, 18 F-FDG PET imaging successfully differentiated the FGFRi-sensitive tumor xenografts from primary or acquired resistant ones by the tumor 18 F-FDG accumulation change upon FGFRi treatment.Of note, both 18 F-FDG tumor accumulation and HK2 expression could respond the administration/withdrawal of FGFRi in NCI-H1581 xenografts correspondingly. Conclusion:The novel association between the molecular mechanism (FGFR/mTOR/HK2 axis) and radiological phenotype ( 18 F-FDG PET uptake) of FGFR-targeted therapy was demonstrated in multiple preclinical models.The adoption of 18 F-FDG PET biomarker-based imaging strategy to assess response/resistance to FGFR inhibition may benefit treatment selection for cancer patients.
Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure
Authors: Zhen-Zhen Lai, Yun Wang, Wen-Jie Zhou, Zhou Liang, Jia-Wei Shi, Hui-Li Yang, Feng Xie, Wei-Dong Chen, Rui Zhu, Ce Zhang, Jie Mei, Jian-Yuan Zhao, Jiang-Feng Ye, Tao Zhang, Ming-Qing Li
Journal: Theranostics (2022)

Introduction: Despite great advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) cannot be effectively avoided.Notably, cellular characteristics and communication that regulate endometrial receptivity and differentiation, and its disorders in RIF at window of implantation (WOI) remain rudimentary.Objectives: In this study, we profiled the endometrial cells present at the WOI timing in RIF patients and healthy controls using single-cell RNA sequencing (scRNA-seq) and provided a detailed molecular and cellular map of a healthy and RIF endometrium at the WOI.Method: In the current study, the endometrium from RIF patient (n = 6; age range, 32 -35 years) and control (Ctrl) (n = 3; age range, 29 -35 years) groups were studied at a single-cell resolution.single-cell RNA-seq and analysis were performed on the endometrium of patients with RIF and Ctrl.Immunofluorescence, flow cytometry assays, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify cellular identity and function.Results: We profiled the transcriptomes of 60222 primary human endometrial cells isolated from control and RIF patients at a single-cell resolution.We discovered dramatic differential expression of endometrial receptivity-related genes in four major endometrial fibroblast-like cells from RIF patients compared to the control endometrium.We observed that CD49a + CXCR4 + NK cells were diminished in proportion with RIF.The decrease in subset of CD63 high PGR high endometrial epithelial cells with high levels of progesterone receptor, autophagy and exosomes should contribute to the decrease in subset of NK cells.Additionally, we characterized aberrant molecular and cellular characteristics and endometrial cell-cell communication disorders in RIF patients.
m<sup>6</sup>A-induced lncDBET promotes the malignant progression of bladder cancer through FABP5-mediated lipid metabolism
Authors: Peihua Liu, Benyi Fan, Belaydi Othmane, Jiao Hu, Huihuang Li, Yu Cui, Zhenyu Ou, Jinbo Chen, Xiongbing Zu
Journal: Theranostics (2022)

The limited effect of adjuvant therapy for advanced bladder cancer (BCa) leads to a poor prognosis.Increasing evidence has shown that RNA N6-methyladenosine (m 6 A) modification plays important functional roles in tumorigenesis.Nevertheless, the role and mechanism of m6A-modified noncoding RNAs (ncRNAs) in BCa remain largely unknown.Methods: RT-PCR, western blotting and ONCOMINE dataset were used to determine the dominant m 6 A-related enzyme in BCa.M 6 A-lncRNA epitranscriptomic microarray was used to screen candidate targets of METTL14.RT-PCR, MeRIP and TCGA dataset were carried out to confirm the downstream target of METTL14.CHIRP/MS was conducted to identify the candidate proteins binding to lncDBET.RT-PCR, western blotting, RIP and KEGG analysis were used to confirm the target of lncDBET.The levels of METTL14, lncDBET and FABP5 were tested in vitro and in vivo.CCK-8, EdU, transwell and flow cytometry assays were performed to determine the oncogenic function of METTL14, lncDBET and FABP5, and their regulatory networks.Results: We identified that the m 6 A level of total RNA was elevated and that METTL14 was the dominant m6A-related enzyme in BCa.m 6 A modification mediated by METTL14 promoted the malignant progression of BCa by promoting the expression of lncDBET.Upregulated lncDBET activated the PPAR signalling pathway to promote the lipid metabolism of cancer cells through direct interaction with FABP5, thus promoting the malignant progression of BCa in vitro and in vivo.Conclusions: Our study establishes METTL14/lncDBET/FABP5 as a critical oncogenic axis in BCa.
Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies
Authors: Hongjian Li, Kun Peng, Kai Yang, Wenbo Ma, Shaolong Qi, Xinyang Yu, Jia He, Xin Lin, Guocan Yu
Journal: Theranostics (2022)

Rationale: Messenger RNA (mRNA) vaccine outperforms other kinds of cancer immunotherapy due to its high response rates, easy preparation, and wide applicability, which is considered as one of the most promising forms of next-generation cancer therapies.However, the inherent instability and insufficient protein expression duration of mRNA limit the efficacy and widespread application of the vaccine.Methods: Here, we first tested the possibility of a novel circular RNA (circRNA) platform for protein expression and compare its duration with linear RNA.Then, we developed a lipid nanoparticle (LNP) system for circRNA delivery in vitro and in vivo.Next, the innate and adaptive immune response of circRNA-LNP complex was evaluated in vivo.The anti-tumor efficacy of circRNA-LNP was further confirmed in three tumor models.Finally, the possibility of combination therapy with circRNA-LNP and adoptive cell transfer therapy was further investigated in a late-stage tumor model. Results:We successfully increased the stability of the RNA vaccine by circularizing the linear RNA molecules to form highly stable circRNA molecules which exhibited durable protein expression ability.By encapsulating the antigen-coding circRNA in LNP enabling in vivo expression, we established a novel circRNA vaccine platform, which was capable of triggering robust innate and adaptive immune activation and showed superior anti-tumor efficacy in multiple mouse tumor models.Conclusions: Overall, our circRNA vaccine platform provides a novel prospect for the development of cancer RNA vaccines in a wide range of hard-to-treat malignancies.
Targeted delivery of nanomedicines for promoting vascular regeneration in ischemic diseases
Authors: Jie Zhuang, Xiangyun Zhang, Qiqi Liu, Mingsheng Zhu, Xinglu Huang
Journal: Theranostics (2022)

Ischemic diseases, the leading cause of disability and death, are caused by the restriction or blockage of blood flow in specific tissues, including ischemic cardiac, ischemic cerebrovascular and ischemic peripheral vascular diseases. The regeneration of functional vasculature network in ischemic tissues is essential for treatment of ischemic diseases. Direct delivery of pro-angiogenesis factors, such as VEGF, has demonstrated the effectiveness in ischemic disease therapy but suffering from several obstacles, such as low delivery efficacy in disease sites and uncontrolled modulation. In this review, we summarize the molecular mechanisms of inducing vascular regeneration, providing the guidance for designing the desired nanomedicines. We also introduce the delivery of various nanomedicines to ischemic tissues by passive or active targeting manner. To achieve the efficient delivery of nanomedicines in various ischemic diseases, we highlight targeted delivery of nanomedicines and controllable modulation of disease microenvironment using nanomedicines.
Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies
Authors: Maimonah Eissa Al-Masawa, Mohammed Abdullah Alshawsh, Chiew Yong Ng, Angela Min Hwei Ng, Jhi Biau Foo, Ubashini Vijakumaran, Revatyambigai Subramaniam, Nur Azurah Abdul Ghani, Kenneth Whitaker Witwer, Jia Xian Law
Journal: Theranostics (2022)

Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We conducted a systematic review of the available evidence to assess sEV therapeutic efficacy and safety in wound healing and skin regeneration in animal models. 68 studies were identified in Web of Science, Scopus, and PubMed that satisfied a set of prespecified inclusion criteria. We critically analyzed the quality of studies that satisfied our inclusion criteria, with an emphasis on methodology, reporting, and adherence to relevant guidelines (including MISEV2018 and ISCT criteria). Overall, our systematic review and meta-analysis indicated that sEV interventions promoted skin regeneration in diabetic and non-diabetic animal models and influenced various facets of the healing process regardless of cell source, production protocol and disease model. The EV source, isolation methods, dosing regimen, and wound size varied among the studies. Modification of sEVs was achieved mainly by manipulating source cells via preconditioning, nanoparticle loading, genetic manipulation, and biomaterial incorporation to enhance sEV therapeutic potential. Evaluation of potential adverse effects received only minimal attention, although none of the studies reported harmful events. Risk of bias as assessed by the SYRCLE's ROB tool was uncertain for most studies due to insufficient reporting, and adherence to guidelines was limited. In summary, sEV therapy has enormous potential for wound healing and skin regeneration. However, reproducibility and comprehensive evaluation of evidence are challenged by a general lack of transparency in reporting and adherence to guidelines. Methodological rigor, standardization, and risk analysis at all stages of research are needed to promote translation to clinical practice.
Cerenkov luminescence imaging of interscapular brown adipose tissue using a TSPO-targeting PET probe in the UCP1 ThermoMouse
Authors: Seok-Yong Lee, Ho Rim Oh, Young-Hwa Kim, Sung-Hwan Bae, Yongseok Lee, Yun-Sang Lee, Byung Chul Lee, Gi Jeong Cheon, Keon Wook Kang, Hyewon Youn
Journal: Theranostics (2022)

Rationale: [ 18 F]fluorodeoxyglucose-positron emission tomography ([ 18 F]FDG-PET) has been widely used as an imaging technique to measure interscapular brown adipose tissue (iBAT) activity.However, it is challenging to obtain iBAT-specific images using [ 18 F]FDG-PET because increased uptake of [ 18 F]FDG is observed in tumors, muscle, and inflamed tissues.Uncoupling protein 1 (UCP1) in the mitochondrial membrane, a well-known molecular marker of BAT, has been proposed as a useful BAT imaging marker.Recently, the UCP1 ThermoMouse was developed as a reporter mouse for monitoring UCP1 expression and investigating BAT activation.In addition, Translocator protein-18 kDa (TSPO) located in the outer mitochondrial membrane is also overexpressed in BAT, suggesting that TSPO-targeting PET has potential for iBAT imaging.However, there are no studies monitoring BAT using TSPO-targeting PET probes in the UCP1 ThermoMouse.Moreover, the non-invasive Cerenkov luminescence imaging (CLI) using Cerenkov radiation from the PET probe has been proposed as an alternative option for PET as it is less expensive and user-friendly.Therefore, we selected [ 18 F]fm-PBR28-d2 as a TSPO-targeting PET probe for iBAT imaging to evaluate the usefulness of CLI in the UCP1 ThermoMouse.Methods: UCP1 ThermoMouse was used to monitor UCP1 expression.Western blotting and immunohistochemistry were performed to measure the level of protein expression.[ 18 F]fm-PBR28-d2 and [ 18 F]FDG were used as radioactive probes for iBAT imaging.PET images were acquired with SimPET, and optical images were acquired with IVIS 100.Results: UCP1 ThermoMouse showed that UCP1 and TSPO expressions were correlated in iBAT.In both PET and CLI, the TSPO-targeting probe [ 18 F]fm-PBR28-d2 was superior to [ 18 F]FDG for acquiring iBAT images.The high molar activity of the probe was essential for CLI and PET imaging.We tested the feasibility of TSPO-targeting probe under cold exposure by imaging with TSPO-PET/CLI.Both signals of iBAT were clearly increased after cold stimulation.Under prolonged isoflurane anesthesia, TSPO-targeting images showed higher signals from iBAT in the short-term than in long-term groups. Conclusion:We demonstrated that TSPO-PET/CLI reflected UCP1 expression in iBAT imaging better than [ 18 F]FDG-PET/CLI under the various conditions.Considering convenience and cost, TSPO-CLI could be used as an alternative TSPO-PET technique for iBAT imaging.
Small extracellular vesicles isolation and separation: Current techniques, pending questions and clinical applications
Authors: Yuanwang Jia, Li Yu, Tieliang Ma, Wenrong Xu, Hui Qian, Yaoxiang Sun, Hui Shi
Journal: Theranostics (2022)

Extracellular vesicles, especially small extracellular vesicles (sEVs) are now accepted as important messengers in cell-to-cell communication and as a promising drug delivery platform.They are involved in nearly all physiological and pathological processes and are involved in disease diagnosis and therapy.However, their heterogeneity of physicochemical properties and functions is not fully understood, which hinders further clinical applications.To obtain highly bioactive sEVs with both high yield and purity, will certainly facilitate their future study and application.This review informs up-to-date research on frequently-used and cutting-edge technologies of sEVs isolation and makes a deep comparison and analysis of different methods, including their advantages, limitations and applications.Pending questions about the inherent property of these small vesicles as well as isolation strategies are discussed.Additionally, an overview of their applications in disease diagnosis and treatment, including some of the on-going clinical trials, are also reviewed.
Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy
Authors: Zaoqu Liu, Zhaokai Zhou, Qin Dang, Hui Xu, Jinxiang Lv, Huanyun Li, Xinwei Han
Journal: Theranostics (2022)

Chimeric antigen receptor (CAR)-T cell therapy represents a landmark advance in personalized cancer treatment.CAR-T strategy generally engineers T cells from a specific patient with a new antigen-specificity, which has achieved considerable success in hematological malignancies, but scarce benefits in solid tumors.Recent studies have demonstrated that tumor immune microenvironment (TIME) cast a profound impact on the immunotherapeutic response.The immunosuppressive landscape of TIME is a critical obstacle to the effector activity of CAR-T cells.Nevertheless, every cloud has a silver lining.The immunosuppressive components also shed new inspiration on reshaping a friendly TIME by targeting them with engineered CARs.Herein, we summarize recent advances in disincentives of TIME and discuss approaches and technologies to enhance CAR-T cell efficacy via addressing current hindrances.Simultaneously, we firmly believe that by parsing the immunosuppressive components of TIME, rationally manipulating the complex interactions of immunosuppressive components, and optimizing CAR-T cell therapy for each patient, the CAR-T cell immunotherapy responsiveness for solid malignancies will be substantially enhanced, and novel therapeutic targets will be revealed.